Daunorubicin is biotransformed anaerobically by rat liver microsomes with a reduced nicotinamide adenine dinucleotide phosphate-generating system to form a series of aglycones. The first reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7-deoxyaglycone, is followed by reduction of the C-13 keto group. The 7-hydroxyaglycone may also form by hydrolytic cleavage of the amino sugar followed then by the same C-13 keto reduction. These reactions are not inhibited by β-diethylaminoethyldiphenylpropyl acetate, whereas subsequent reactions in the D ring of the aglycones can be completely blocked by this cytochrome P-450 inhibitor: reductive and hydrolytic cleavage of the C-4 methoxy group. Thus, five reactions at three sites are described and theoretical pathways are proposed for the expected 12 aglycones from daunorubicin.

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This project was supported in part by Project Grant CA-24778 from the National Cancer Institute and by a grant from the Gunnar Nilsson Cancer Research Fund.

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